Clinical pharmacology of mecillinam in calves

Abstract

The minimal inhibitory concentrations (MIC) of mecillinam, a novel beta-amidinopenicillanic acid derivative with unusual activity against Gram-negative bacteria, were compared with the MIC of cephazolin, cephalothin, amoxycillin, oxytetracycline, chloramphenicol, dihydrostreptomycin, neomycin, kanamycin, gentamicin and sulfadoxin/trimethoprim (TMP) against pathogenic Gram-negative bacteria recovered from neonatal calves. The MIC values of mecillinam ranged between 0.05 microgram/ml and 12.5 micrograms/ml, and the MIC90 values were 1.56 micrograms/ml and 3.12 micrograms/ml. The activity of mecillinam against salmonella, Escherichia coli and Pasteurella multocida was similar to or slightly greater than the activities of the first-generation cephalosporins, gentamicin and sulfa/TMP. Mecillinam concentrations less than or equal to 3.12 micrograms/ml inhibited the growth of the majority of isolates which were resistant (MIC90 greater than 100 micrograms/ml) to the other antibiotics studied. The minimum bactericidal concentration (MBC) values of mecillinam were two- to three-fold higher than the MIC values. The two-compartment open model was appropriate for the analysis of serum mecillinam concentrations measured after intravenous administration. The distribution half-life (t1/2 alpha) was 11.7 min, the elimination half-life (t1/2 beta) was 53.3 min, and the apparent volume of distribution (Vd (area)) and the distribution volume at steady state (Vd (ss)) were 0.568 and 0.896 l/kg, respectively. The drug was quickly absorbed after intramuscular (i.m.) injection; peak serum drug concentrations were directly related to the dose administered. They were obtained 30 min after treatment and the i.m. t1/2 was approximately 65 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Pharmacology of Cefazolin in Calves

“…injection is also characteristic for aqueous solutions of these drugs. Serum Cmax values for cefazolin in calves after i. v. and i. m. administration were, however, considerably higher than those of other p-lactam antibiotics, like ampicillin, amoxycillin (24), mecillinam (14) and cephacetrile (25) administered at equal doses. Additionally, the calculated Vd' of cefazolin in calves ( Table 2) was considerably smaller than the Vd' of ampicillin, amoxycillin, mecillinam and cephacetrile.…”

Probenecid effect on cefuroxime pharmacokinetics in calves

“…appeared to be more sensitive to cefuroxime activity. The second generation cephalosporins, except for cefaclor, do not seem to be antimicrobially more active against the pathogens mentioned above than the first generation compounds (Soback et al, 1986;Soback et al, 1987;Soback, 1988) while ceftriaxone, a third generation cephalosporin, had 10-500 times lower M I C g~ values against these pathogens compared to the earlier generations (Soback & Ziv, 1988).…”

“…Because of the apparent vulnerability of new-born calves to bacterial infections, antimicrobial agents are given extensively to these animals. It appears, however, that many Gram-negative pathogens are becoming increasingly resistant to many of the presently used antibiotics (Soback et al, 1986) necessitating a search for other effective therapeutic agents. Because of the low toxicity of the cephalosporin antibiotics they are well suited for use in neonatal animals.…”

Pharmacokinetics of single doses of cefoxitin given by the intravenous and intramuscular routes to unweaned calves

“…Cefoxitin has been shown to penetrate cephalosporins tend to be more active against readily tissue fluid (Gillett & Wise, 1978), bile, milk (Geddes et al, 1977), ascitic fluid (Heseltine et al, 1977), and lung tissue (Perea et al, 1983). Cefoxitin has, therefore, the potential to be clinically valuable in treatment of neonatal calf diseases, such as diarrhoea, pneumonia etc., which are often caused by Gram-negative bacteria resistant to many of the commonly used antibiotics (Soback et al, 1986).…”